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Published in: Acta Neuropathologica 4/2005

01-10-2005 | Regular Paper

Time course changes of estrogen receptor α expression in the adult rat hippocampus after kainic acid-induced status epilepticus

Authors: Daisuke Tokuhara, Toshiaki Yokoi, Ryouichi Nakajima, Hideji Hattori, Osamu Matsuoka, Tsunekazu Yamano

Published in: Acta Neuropathologica | Issue 4/2005

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Abstract

Although estrogens possess neuroprotective and epileptogenic properties, the expression pattern of the estrogen receptor (ER) following status epilepticus (SE) remains unclear. We therefore examined the expression pattern of ERα in the adult rat hippocampus after SE. SE was induced in rats by kainic acid (KA; 12 mg/kg, i.p.). ERα expression was assessed by immunostaining and Western blotting at various times (24 h, and 7, 14, and 21 days) after SE onset. Immunohistochemistry disclosed ERα expression in the CA1 and CA3 pyramidal cells of control rats, whereas, after SE, ERα-immunoreactive neurons decreased in number due to neuronal death in the CA1 from days 7 to 21. On the other hand, ERα-immunoreactive cells with astrocytic morphology were observed in the CA1 beginning on day 7 after SE. This immunoreactivity increased in proportion to the hypertrophy of astrocytes up to day 21. Western blotting revealed a significant decrease in ERα expression on day 7 after SE in comparison with control level. However, ERα expression on days 14 and 21 were similar when comparing KA-treated and control rats. These results indicate that reactive astrocytes are important sites of estrogen action in the hippocampal CA1 after SE.
Literature
1.
go back to reference Broman J, Hassel B, Rinvik E, Ottersen OP (2000) Biochemistry and anatomy of transmitter glutamate. In: Ottersen OP, Storm-Mathisen J (eds) Glutamate. Elsevier Science, Amsterdam, pp 1–44 Broman J, Hassel B, Rinvik E, Ottersen OP (2000) Biochemistry and anatomy of transmitter glutamate. In: Ottersen OP, Storm-Mathisen J (eds) Glutamate. Elsevier Science, Amsterdam, pp 1–44
2.
go back to reference Buterbaugh GG (1987) Acquisition of amygdale-kindled seizure in female rats: relationship between the effect of estradiol and intraamygdaloid electrode location. Pharmacol Biochem Behav 28:291–297CrossRefPubMed Buterbaugh GG (1987) Acquisition of amygdale-kindled seizure in female rats: relationship between the effect of estradiol and intraamygdaloid electrode location. Pharmacol Biochem Behav 28:291–297CrossRefPubMed
3.
go back to reference Buterbaugh GG (1988) Postictal events in amygdala-kindled female rats with and without estradiol replacement. Exp Neurol 95:697–713CrossRef Buterbaugh GG (1988) Postictal events in amygdala-kindled female rats with and without estradiol replacement. Exp Neurol 95:697–713CrossRef
4.
go back to reference De Lanerolle NC, Kim JH, Williamson A, et al (2003) A retrospective analysis of hippocampal pathology in human temporal lobe epilepsy: evidence for distinctive patient subcategories. Epilepsia 44:677–687CrossRefPubMed De Lanerolle NC, Kim JH, Williamson A, et al (2003) A retrospective analysis of hippocampal pathology in human temporal lobe epilepsy: evidence for distinctive patient subcategories. Epilepsia 44:677–687CrossRefPubMed
5.
go back to reference Dubal DB, Shughrue PJ, Wilson ME, Merchenthaler I, Wise PM (1999) Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors. J Neurosci 19:6385–6393PubMed Dubal DB, Shughrue PJ, Wilson ME, Merchenthaler I, Wise PM (1999) Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors. J Neurosci 19:6385–6393PubMed
6.
go back to reference During MJ, Spencer DD (1993) Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet 341:1607–1610CrossRefPubMed During MJ, Spencer DD (1993) Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet 341:1607–1610CrossRefPubMed
7.
go back to reference Eid T, Thomas MJ, Spencer DD, Runden-Pran E, Lai JC, Malthankar GV, Kim JH, Danbolt NC, Ottersen OP, De Lanerolle NC (2004) Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. Lancet 363:28–37CrossRefPubMed Eid T, Thomas MJ, Spencer DD, Runden-Pran E, Lai JC, Malthankar GV, Kim JH, Danbolt NC, Ottersen OP, De Lanerolle NC (2004) Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. Lancet 363:28–37CrossRefPubMed
8.
go back to reference Garcia-Segura LM, Chowen JA, Parducz A, Naftolin F (1994) Gonadal hormones as promoters of structural synaptic plasticity: cellular mechanisms. Progr Neurobiol 44:279–307CrossRefPubMed Garcia-Segura LM, Chowen JA, Parducz A, Naftolin F (1994) Gonadal hormones as promoters of structural synaptic plasticity: cellular mechanisms. Progr Neurobiol 44:279–307CrossRefPubMed
9.
go back to reference Garcia-Segura LM, Luquin S, Parducz A, Naftolin F (1994) Gonadal hormone regulation of glial fibrillary acidic protein immunoreactivity and glial ultrastructure in the rat neuroendocrine hypothalamus. Glia 10:59–69CrossRefPubMed Garcia-Segura LM, Luquin S, Parducz A, Naftolin F (1994) Gonadal hormone regulation of glial fibrillary acidic protein immunoreactivity and glial ultrastructure in the rat neuroendocrine hypothalamus. Glia 10:59–69CrossRefPubMed
10.
go back to reference Garcia-Ovejero D, Veiga S, Garcia-Segura LM, Doncarlos LL (2002) Glial expression of estrogen and androgen receptors after rat brain injury. J Comp Neurol 450:256–271CrossRefPubMed Garcia-Ovejero D, Veiga S, Garcia-Segura LM, Doncarlos LL (2002) Glial expression of estrogen and androgen receptors after rat brain injury. J Comp Neurol 450:256–271CrossRefPubMed
11.
go back to reference Hoffman GE, Moore N, Fiskum G, Murphy AZ (2003) Ovarian steroid modulation of seizure severity and hippocampal cell death after kainic acid treatment. Exp Neurol 181:124–134CrossRef Hoffman GE, Moore N, Fiskum G, Murphy AZ (2003) Ovarian steroid modulation of seizure severity and hippocampal cell death after kainic acid treatment. Exp Neurol 181:124–134CrossRef
12.
go back to reference Hu XY, Qin S, Lu YP, Ravid R, Swaab DF, Zhou JN (2003) Decreased estrogen receptor-α expression in hippocampal neurons in relation to hyperphosphorylated tau in Alzheimer patients. Acta Neuropathol 106:213–220CrossRefPubMed Hu XY, Qin S, Lu YP, Ravid R, Swaab DF, Zhou JN (2003) Decreased estrogen receptor-α expression in hippocampal neurons in relation to hyperphosphorylated tau in Alzheimer patients. Acta Neuropathol 106:213–220CrossRefPubMed
13.
go back to reference Jover T, Tanaka H, Calderone A, Oguro K, Bennett MV, Etgen AM, Zukin RS (2002) Estrogen protects against global ischemia-induced neuronal death and prevents activation of apoptotic signaling cascades in the hippocampal CA1. J Neurosci 22:2115–2124PubMed Jover T, Tanaka H, Calderone A, Oguro K, Bennett MV, Etgen AM, Zukin RS (2002) Estrogen protects against global ischemia-induced neuronal death and prevents activation of apoptotic signaling cascades in the hippocampal CA1. J Neurosci 22:2115–2124PubMed
14.
go back to reference Levin-Allerhand J, McEwen BS, Lominska CE, Lubahn DB, Korach KS, Smith JD (2001) Brain region-specific up-regulation of mouse apolipoprotein E by pharmacological estrogen treatments. J Neurochem 79:796–803CrossRefPubMed Levin-Allerhand J, McEwen BS, Lominska CE, Lubahn DB, Korach KS, Smith JD (2001) Brain region-specific up-regulation of mouse apolipoprotein E by pharmacological estrogen treatments. J Neurochem 79:796–803CrossRefPubMed
15.
go back to reference Lu YP, Zeng M, Hu XY, Xu H, Swaab DF, Ravid R, Zhou JN (2003) Estrogen receptor α-immunoreactive astrocytes are increased in the hippocampus in Alzheimers’ disease. Exp Neurol 183:482–488CrossRefPubMed Lu YP, Zeng M, Hu XY, Xu H, Swaab DF, Ravid R, Zhou JN (2003) Estrogen receptor α-immunoreactive astrocytes are increased in the hippocampus in Alzheimers’ disease. Exp Neurol 183:482–488CrossRefPubMed
16.
go back to reference Mathern GW, Babb TL, Armstrong DL (1997) Hippocampal sclerosis. In: Engel JJ, Pedley TA (eds) Epilepsy: acomprehensive textbook. Lippincott-Raven, Philadelphia, pp 133–155 Mathern GW, Babb TL, Armstrong DL (1997) Hippocampal sclerosis. In: Engel JJ, Pedley TA (eds) Epilepsy: acomprehensive textbook. Lippincott-Raven, Philadelphia, pp 133–155
17.
go back to reference Mingkow L, Pfaff DW (1985) Estrogen effects on neuronal responsiveness to electrical and neurotransmitter stimulation: an in-vitro study on the ventromedial nucleus of the hypothalamus. Brain Res 347:1–10CrossRefPubMed Mingkow L, Pfaff DW (1985) Estrogen effects on neuronal responsiveness to electrical and neurotransmitter stimulation: an in-vitro study on the ventromedial nucleus of the hypothalamus. Brain Res 347:1–10CrossRefPubMed
18.
go back to reference Newmark ME, Penry JK (1980) Catamenial epilepsy. Epilepsia 21:282–300 Newmark ME, Penry JK (1980) Catamenial epilepsy. Epilepsia 21:282–300
19.
go back to reference Paganini-Hill A, Henderson VW (1996) Estrogen replacement therapy and risk of Alzheimer disease. Arch Intern Med 156:2213–2217CrossRefPubMed Paganini-Hill A, Henderson VW (1996) Estrogen replacement therapy and risk of Alzheimer disease. Arch Intern Med 156:2213–2217CrossRefPubMed
20.
go back to reference Ramirez AD, Liu X, Menniti FS (2003) Repeated estradiol treatment prevents MPTP-induced dopamine depletion in male mice. Neuroendocrinology 77:223–231CrossRefPubMed Ramirez AD, Liu X, Menniti FS (2003) Repeated estradiol treatment prevents MPTP-induced dopamine depletion in male mice. Neuroendocrinology 77:223–231CrossRefPubMed
21.
go back to reference Reibel S, Andre V, Chassagnon S, Andre G, Marescaux C, Nehlig A, Depaulis A (2000) Neuroprotective effects of chronic estradiol benzoate treatment on hippocampal cell loss induced by status epilepticus in the female rat. Neurosci Lett 281:79–82CrossRefPubMed Reibel S, Andre V, Chassagnon S, Andre G, Marescaux C, Nehlig A, Depaulis A (2000) Neuroprotective effects of chronic estradiol benzoate treatment on hippocampal cell loss induced by status epilepticus in the female rat. Neurosci Lett 281:79–82CrossRefPubMed
22.
go back to reference Rune GM, Wehrenberg U, Prange-Kiel J, Zhou L, Adelmann G, Frotscher M (2002) Estrogen up-regulates estrogen receptor α and synaptophysin in slice cultures of rat hippocampus. Neuroscience 113:167–175CrossRefPubMed Rune GM, Wehrenberg U, Prange-Kiel J, Zhou L, Adelmann G, Frotscher M (2002) Estrogen up-regulates estrogen receptor α and synaptophysin in slice cultures of rat hippocampus. Neuroscience 113:167–175CrossRefPubMed
23.
go back to reference Saberi M, Pourgholami MH, Jorjani M (2001) The acute effects of estradiol benzoate on amygdale-kindled seizures in male rats. Brain Res 891:1–6CrossRefPubMed Saberi M, Pourgholami MH, Jorjani M (2001) The acute effects of estradiol benzoate on amygdale-kindled seizures in male rats. Brain Res 891:1–6CrossRefPubMed
24.
go back to reference Sandra L, Stitt MS, Kinnard WJ (1968) The effects of certain progestins and estrogens on the threshold of electrically induced seizure patterns Neurology 18:213–216 Sandra L, Stitt MS, Kinnard WJ (1968) The effects of certain progestins and estrogens on the threshold of electrically induced seizure patterns Neurology 18:213–216
25.
go back to reference Sato K, Matsuki N, Ohno Y, Nakazawa K (2003) Estrogens inhibitl-glutamate uptake activity of astrocytes via membrane estrogen receptor alpha. J Neurochem 86:1498–505CrossRefPubMed Sato K, Matsuki N, Ohno Y, Nakazawa K (2003) Estrogens inhibitl-glutamate uptake activity of astrocytes via membrane estrogen receptor alpha. J Neurochem 86:1498–505CrossRefPubMed
26.
go back to reference Solum DT, Handa RJ (2001) Localization of estrogen receptor alpha (ERα) in pyramidal neurons of the developing rat hippocampus. Dev Brain Res 128:165–175CrossRef Solum DT, Handa RJ (2001) Localization of estrogen receptor alpha (ERα) in pyramidal neurons of the developing rat hippocampus. Dev Brain Res 128:165–175CrossRef
27.
go back to reference Spencer DD (1994) Classifying the epilepsies by substrate. Clin Neurosci 2:104–109 Spencer DD (1994) Classifying the epilepsies by substrate. Clin Neurosci 2:104–109
28.
go back to reference Stoltzner SE, Berchtold NC, Cotman CW, Pike CJ (2001) Estrogen regulates bcl-x expression in rat hippocampus. Neuroreport 12:2797–2800CrossRefPubMed Stoltzner SE, Berchtold NC, Cotman CW, Pike CJ (2001) Estrogen regulates bcl-x expression in rat hippocampus. Neuroreport 12:2797–2800CrossRefPubMed
29.
go back to reference Stone DJ, Song Y, Anderson CP, Krohn KK, Finch CE, Rozovsky I (1998) Bidirectional transcription regulation of glial fibrillary acidic protein by estradiol in vivo and in vitro. Endocrinology 139:3202–3209CrossRefPubMed Stone DJ, Song Y, Anderson CP, Krohn KK, Finch CE, Rozovsky I (1998) Bidirectional transcription regulation of glial fibrillary acidic protein by estradiol in vivo and in vitro. Endocrinology 139:3202–3209CrossRefPubMed
30.
go back to reference Su JD, Qiu J, Zhong YP, Li XY, Wang JW, Chen YZ (2001) Expression of estrogen receptor (ER)-α and -β immunoreactivity in hippocampal cell cultures with special attention to GABAergic neurons. J Neurosci Res 65:396–402CrossRefPubMed Su JD, Qiu J, Zhong YP, Li XY, Wang JW, Chen YZ (2001) Expression of estrogen receptor (ER)-α and -β immunoreactivity in hippocampal cell cultures with special attention to GABAergic neurons. J Neurosci Res 65:396–402CrossRefPubMed
31.
go back to reference Tang MX, Jacobs D, Stern Y, Marder K, Schofield P, Gurland B, Andrews H, Mayeux R (1996) Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet 348:429–432CrossRefPubMed Tang MX, Jacobs D, Stern Y, Marder K, Schofield P, Gurland B, Andrews H, Mayeux R (1996) Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet 348:429–432CrossRefPubMed
32.
go back to reference Toran-Allerand CD, Guan X, MacLusky NJ, Horvath TL, Diano S, Singh M, Connolly ES Jr, Nethrapalli IS, Tinnikov AA (2002) ER-X: a novel, plasma membrane-associated, putative estrogen receptor that is regulated during development and after ischemic brain injury. J Neurosci 22:8391–8401PubMed Toran-Allerand CD, Guan X, MacLusky NJ, Horvath TL, Diano S, Singh M, Connolly ES Jr, Nethrapalli IS, Tinnikov AA (2002) ER-X: a novel, plasma membrane-associated, putative estrogen receptor that is regulated during development and after ischemic brain injury. J Neurosci 22:8391–8401PubMed
33.
go back to reference Velisek L, Moshe SL (2003) Temporal lobe epileptogenesis and epilepsy in the developing brain: bridging the gap between the laboratory and the clinic. Progression, but in what direction? Epilepsia 44 (Suppl 12):S51–S59CrossRef Velisek L, Moshe SL (2003) Temporal lobe epileptogenesis and epilepsy in the developing brain: bridging the gap between the laboratory and the clinic. Progression, but in what direction? Epilepsia 44 (Suppl 12):S51–S59CrossRef
34.
go back to reference Velisek L, Veliskova J (2002) Estrogen treatment protects GABA(B) inhibition in the dentate gyrus of female rats after kainic acid-induced status epilepticus. Epilepsia 43 (Suppl 5):S146–S151CrossRef Velisek L, Veliskova J (2002) Estrogen treatment protects GABA(B) inhibition in the dentate gyrus of female rats after kainic acid-induced status epilepticus. Epilepsia 43 (Suppl 5):S146–S151CrossRef
35.
go back to reference Veliskova J, Velisek L, Galanopoulou AS, Sperber EF (2000) Neuroprotective effects of estrogens on hippocampal cells in adult female rats after status epilepticus. Epilepsia 41: S30–S35CrossRef Veliskova J, Velisek L, Galanopoulou AS, Sperber EF (2000) Neuroprotective effects of estrogens on hippocampal cells in adult female rats after status epilepticus. Epilepsia 41: S30–S35CrossRef
36.
go back to reference Weiland NG, Orikasa C, Hayashi S, McEwen BS (1997) Distribution and hormone regulation of estrogen receptor immunoreactive cells in the hippocampus of male and female rats. J Comp Neurol 388:603–612CrossRefPubMed Weiland NG, Orikasa C, Hayashi S, McEwen BS (1997) Distribution and hormone regulation of estrogen receptor immunoreactive cells in the hippocampus of male and female rats. J Comp Neurol 388:603–612CrossRefPubMed
Metadata
Title
Time course changes of estrogen receptor α expression in the adult rat hippocampus after kainic acid-induced status epilepticus
Authors
Daisuke Tokuhara
Toshiaki Yokoi
Ryouichi Nakajima
Hideji Hattori
Osamu Matsuoka
Tsunekazu Yamano
Publication date
01-10-2005
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 4/2005
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-005-1071-z

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